Selenium Deficiency Impairs The Biosynthesis Of Prostacyclin In Rat Aorta

H Bult, P Van den Bosch, R Von den Bossche, A Van Hoydonck, A Herman
1981 Thrombosis and Haemostasis  
Prostacyclin(PGI2)synthase is inactivated by lipidhydroperoxides and it has been suggested that this occurs in atheromatous plaques (S.Moncada & J.R.Vane, New Engl. J.Med.,300,ll42,1979). Glutathione peroxidase is a selenium(Se) containing enzyme which converts hydroperoxides to less toxic alcohols. Therefore, we investigated whether Se deficiency reduced the biosynthesis of PGI2. Rats were fed a diet with a reduced Se content(25 ppb) or a standard diet (l42 ppb Se). After 7months 4 rats from
more » ... onths 4 rats from each group were killed. Urinary Se-excretion and Se content of the liver were significantly (P<0.05, Student-t test) reduced. Aorta's were removed and rings (about 2 mg) were stirred in l ml Krebs'solution. After 5 and 15 min, the release of endogenous PGI2 into the medium was assessed by its anti-aggregating capacity in rabbit platelet rich plasma and after 16 min the 6-oxo-PGF1α content of the medium was measured with RIA. Se deficient aorta's released less PGI2 like activity (at 5 min, 46 % reduction, P<0.05; at 15 min, 25 % reduction) and less 6-oxo- PGFia (43% reduction, P<0.05). Similar experiments were performed with rings that were exhausted by 6 h preincubation in 100ml 50 mMTris, pH 7.5 in the absence of glucose. This procedure reduced the endogenous PGI2 release in control aortic rings with respectively 81 %(bioassay) or 89 % (RIA of 6-oxo-PGF]a). In Se deficient, exhausted rings the endogenous biosynthesis of PGI2 was strongly impaired as indicated by bioassay and measurements of 6-oxo- PGF1α (82 % reduction, P<0.05). Cyclo-oxygenase and PGI2# synthase activities were measured by incubation of 20 mg aorta with respectively 10/ug l-14C-arachidonic acid or 10μg l4C-PGH2. After 20 min the reactions were stopped and ihe products formed were extracted, radiochromatographed and quantified by liquid scintillation counting. In Se deficient aortas, cyclo oxygenase activity was not affected whereas PGl2-synthase activity showed 37 % reduction (P<0.05).These results support the hypothesis that a low peroxide tone is a prerequisite for an optimum biosynthesis of PGI2.
doi:10.1055/s-0038-1652809 fatcat:tk6juvtv2bbwnjskr6a7ktg4qq